June 08, 2026 —
Neurogene announced the successful completion of dosing in the Embolden™ registrational trial of NGN-401, an investigational AAV9 gene therapy being developed as a potential one-time treatment for Rett syndrome.
The company exceeded its original enrollment target by dosing 25 participants, compared with the initial target of 20. The trial’s statistical analysis plan had pre-specified an intent-to-treat population of up to 24 participants, and Neurogene elected to dose all eligible participants already in screening due to strong demand from the Rett syndrome community.
Rett syndrome is a rare neurological disorder primarily affecting girls and is most commonly caused by mutations in the MECP2 gene. NGN-401 is designed to deliver the full-length human MECP2 gene and includes Neurogene’s EXACT™ transgene regulation technology, which is intended to tightly control MeCP2 protein expression on a cell-by-cell basis. This regulation is important because both insufficient and excessive MeCP2 expression can be biologically problematic.
The Embolden trial is a multi-center, single-arm, open-label, baseline-controlled registrational study evaluating a one-time dose of NGN-401 at 1E15 vg in females with Rett syndrome aged three years and older. The therapy is administered by intracerebroventricular delivery to support broad targeting of the brain and nervous system.
The primary endpoint is a composite measure requiring a Clinical Global Impression-Improvement score of ≤3 and a gain from baseline of at least one developmental milestone from a pre-specified list. The primary analysis to support a planned Biologics License Application is expected after the first 24 participants have completed 12 months of follow-up. Topline data from Embolden are anticipated in the second half of 2027.
NGN-401 at the 1E15 vg dose had been generally well tolerated across 35 treated participants in the Phase 1/2 and Embolden trials. Neurogene reported no cases of hemophagocytic lymphohistiocytosis, or HLH, at this dose level.
The registrational trial builds on previously reported interim Phase 1/2 data, which showed multidomain, durable gains and continued developmental milestone acquisitions as of the October 30, 2025 data cutoff. Neurogene plans to present updated interim Phase 1/2 safety and efficacy data, including at least 12 months of follow-up for all 10 participants, in mid-2026.
NGN-401 has received multiple regulatory designations, including FDA Breakthrough Therapy, RMAT, Fast Track, Orphan Drug, Rare Pediatric Disease designations, and selection for the START Pilot Program. It has also received EMA Advanced Therapy Medicinal Product, Orphan, and PRIME designations, as well as the UK MHRA Innovative Licensing and Application Pathway designation.
The completion of dosing in Embolden marks an important milestone for Neurogene and for the Rett syndrome field. If successful, NGN-401 could become one of the most advanced AAV gene therapy programs designed to address the underlying genetic cause of Rett syndrome through regulated MECP2 gene delivery.
